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Utilization of enterobactin and other exogenous iron sources by Haemophilus influenzae, H. parainfluenzae and H.
P Williams1, D J Morton, K J Towner
1Department of Pharmaceutical Sciences, University of Nottingham, UK.
Abstract:
The ability of Haemophilus influenzae, H. parainfluenzae and H. paraphrophilus to utilize iron complexes, iron-proteins and exogenous microbial siderophores was evaluated. In a plate bioassay, all three species used not only ferric nitrate but also the iron chelates ferric citrate, ferric nitrilotriacetate and ferric 2,3-dihydroxybenzoate. Each Haemophilus species examined also used haemin, haemoglobin and haem-albumin as iron sources although only H. influenzae could acquire iron from transferrin or from haemoglobin complexed with haptoglobin. None of the haemophili obtained iron from ferritin or lactoferrin or from the microbial siderophores aerobactin or desferrioxamine B. However, the phenolate siderophore enterobactin supplied iron to both H. parainfluenzae and H. paraphrophilus, and DNA isolated from both organisms hybridized with a DNA probe prepared from the Escherichia coli ferric enterobactin receptor gene fepA. In addition, a monospecific polyclonal antiserum raised against the E. coli 81 kDa ferric enterobactin receptor (FepA) recognized an iron-repressible outer membrane protein (OMP) in H. parainfluenzae of between 80 and 82 kDa (depending on the strain). This anti-FepA serum did not cross-react with any of the OMPs of H. paraphrophilus or H. influenzae. The OMPs of each Haemophilus species were also probed with antisera raised against the 74 kDa Cir or 74 kDa IutA (aerobactin receptor) proteins of E. coli. Apart from one H. parainfluenzae strain (NCTC 10665), in which an OMP of about 80 kDa cross-reacted with the anti-IutA sera, no cross-reactivity was observed between Cir, IutA and the OMPs of H. influenzae, H. parainfluenzae or H. paraphrophilus.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study reveals how Haemophilus species acquire iron, finding they utilize various iron sources like siderophores, but differ in their ability to use iron-binding proteins. Enterobactin is a key iron source for H. parainfluenzae and H. paraphrophilus.
Area of Science:
- Microbiology
- Bacterial Physiology
- Iron Metabolism
Background:
- Iron is essential for bacterial growth and virulence.
- Haemophilus species are important human pathogens.
- Understanding iron acquisition mechanisms is crucial for targeting these bacteria.
Purpose of the Study:
- To investigate the iron utilization capabilities of Haemophilus influenzae, H. parainfluenzae, and H. paraphrophilus.
- To identify specific iron uptake pathways, including the role of siderophores and iron-binding proteins.
Main Methods:
- Plate bioassays to assess iron source utilization.
- DNA hybridization using Escherichia coli ferric enterobactin receptor gene (fepA) probe.
- Western blotting with antisera against E. coli outer membrane proteins (OMPs) like FepA, Cir, and IutA.
Main Results:
- All three Haemophilus species utilized ferric nitrate, citrate, nitrilotriacetate, and 2,3-dihydroxybenzoate.
- Haemin, haemoglobin, and haem-albumin served as iron sources for all species; only H. influenzae used transferrin and haptoglobin-complexed haemoglobin.
- Enterobactin provided iron to H. parainfluenzae and H. paraphrophilus, with evidence of a functional enterobactin receptor (FepA homolog) in these species.
Conclusions:
- Haemophilus species exhibit diverse iron acquisition strategies, utilizing both host-derived iron and microbial siderophores.
- H. parainfluenzae and H. paraphrophilus possess a functional enterobactin uptake system, distinct from H. influenzae's primary mechanisms.
- These findings highlight species-specific adaptations in iron metabolism within the Haemophilus genus.